Herpesviruses evolved over millions of years and are highly disseminated in nature. Members of the family were identified in humans, non-human primates and most other mammals and vertebrates. Herpesviruses are enveloped double stranded DNA viruses, infecting cells that carry negatively charged structures such as heparin sulfate and or glycosaminoglycans, in addition to a herpes viral entry mediator, on their surface. A characteristic feature of these viruses is their ability to remain latent in their host for life after primary infection and to reactivate more or less frequently from a pool of latent infected cells upon diverse internal and external stimuli.
Herpes simplex virus (HSV) can cause severe life-threatening infections in immunocompromised patients and in the neonate, while exhibiting a self-limiting disease in an immunocompetent host. HSV is the major cause of sporadic acute encephalitis in the western world, with a mortality exceeding 70% when untreated. Neonatal HSV infection has a poor prognosis despite antiviral therapy (e.g., acyclovir). Twenty-five percent of infants who contract herpes at delivery will develop a disseminated herpetic infection and suffer a 40% mortality despite antiviral therapy. Accordingly, new ways to treat life-threatening HSV disease are urgently needed.
Even in immunocompetent humans, HSV can cause corneal infection leading to permanent scarring, loss of vision, and blindness. Epithelial keratitis is the most common presentation of ocular infection by HSV. Despite the availability of antivirals and steroids to suppress inflammation associated with acute herpetic disease, chronic HSV continues to cause significant ocular morbidity. Accordingly, new ways to treat HSV ocular disease are urgently needed.